In the society of today there is an increasing demand for products that will improve the physiological visual appearance of human beings.
Chronological age, environmental factors, changes in physiological functions of skin, psoriasis, dermatitis, cellulites, viral and/or bacteriological attacks, are some factors that affect the appearance of human beings in a cosmetically undesirable way.
Many of the alterations mentioned above are caused by changes in the outer epidermal layer of the skin, while others are caused by changes in the lower part of dermis. For instance, chronological age and extensive exposure to environmental factors, such as sun radiation, affect dermis in such way that dermis undergoes structural and functional changes, which result in many of the characteristics of aged skin, such as loss of elasticity, formation of wrinkles, loss of water-holding capacity, uneven distribution of fat, cellulites and sagging.
One thing that these factors have in common is that they are obtained by the loss of blood perfusion in the affected tissues.
Viral and bacteriological attacks may also result in impaired cosmetic appearance. Examples of such viral or bacteriological attack are herpes, such as Herpes Simplex Virus type 1 (HSV-1), Herpes Simplex Virus type 2 (HSV-2), Epstein Barr Virus (EBV), CytoMegaloVirus (CMV), Varicella Zoster Virus (VZV), human herpes virus 6 (exanthum subitum and roseola infantum), human herpes virus 8 (HHV-8), caposis sarcoma, probably caused by HHV-8, genital warts or warts, such as verruca vulgaris, verruca planae, verruca seborroica, filiform warts, mosaic warts, etc., caused by virus, and molluscs, caused by poxvirus. Such attacks lead often to cosmetically unaccepted skin defects, such as scars.
Psoriasis, such as invers psoriasis, psoriasis guttata, psoriasis pustulosa etc., is an inflammatory reaction in the skin, that may appear as a consequence of infection of Streptococcus. The disorder is not a self-healing disorder, and has to be treated, if the person suffering from psoriasis finds the disorder disfiguring or affecting his/her appearance in an undesirable way. Treatment of psoriasis is restricted to anti-inflammatory substances, such as glucocorticosteroids. This kind of treatment is often accompanied by adverse side effects, such as skin atrophy, telangiectasia, striae, hypertrichosis, rosacea, and dermatitis.
Dermatitis is another skin disorder that may disfigure a person, or affect the visual appearance of the person in a negative way.
The techniques according to the prior art, in respect of chronological age, environmental factors, changes in physiological functions of skin, include numerous of physiological, chemical, and mechanical methods, such as treatment with hydroxy acids, retinoids, barrier disrupters, tape stripping, solvent extraction etc. These methods present various drawbacks, such as irritation of the skin, skin toxicity, the requirement of high concentrations of expensive ingredients, pH values that are incompatible with the optimum pH value of the skin, long and cumbersome trials to establish whether or not a specific compound or composition is toxic or not, etc. Furthermore, the majority of the cosmetic methods according to the prior art induce invocation of damage of the skin, which results in the in set of repair mechanisms. Hence, there will be a period of time, such as weeks or months, during which the skin will remain irritated, and after which tolerance sets in and the irritations will diminish.
Up to this point there is no method, composition, compound etc., with the ability to simultaneously treat and prevent cosmetically undesirable disorders originating from both physiological factors, such as chronological age, environmental factors, changes in physiological functions of skin, such as psoriasis, dermatitis, cellulites, etc., and viral and bacteriological attacks.
Nitric oxide (NO) is a highly reactive molecule that is involved in many cell functions. In fact, nitric oxide plays a crucial role in the immune system and is utilized as an effector molecule by macrophages to protect itself against a number of pathogens, such as fungi, viruses, bacteria etc., and general microbial invasion. This improvement of healing is partly caused by NO inhibiting the activation or aggregation of blood platelets, and also by NO causing a reduction of inflammatory processes at the site of an implant.
NO is also known to have an anti-pathogenic, especially an anti-viral, effect, and furthermore NO has an anti-cancerous effect, as it is cytotoxic and cytostatic in suitable concentrations, i.e. it has among other effects tumoricidal and bacteriocidal effects. NO has for instance cytotoxic effects on human haematological malignant cells from patients with leukaemia or lymphoma, whereby NO may be used as a chemotherapeutic agent for treating such haematological disorders, even when the cells have become resistant to conventional anti-cancer drugs. This anti-pathogenic and anti-tumour effect of NO is taken advantage of by the present invention for cosmetic purposes, without having adverse effects.
However, due to the short half-life of NO, it has hitherto been very hard to treat viral, bacteria, virus, fungi or yeast infections with NO. This is because NO is actually toxic in high concentrations and has negative effects when applied in too large amounts to the body.
NO is actually also a vasodilator, and too large amounts of NO cause for instance a complete collapse of the circulatory system. On the other hand, NO has a very short half-life of fractions of a second up to a few seconds, once it is released. Hence, administration limitations due to short half-life and toxicity of NO have been limiting factors in the use of NO in the field of anti-pathogenic and anti-cancerous treatment so far.
In recent years research has been directed to polymers with the capability of releasing nitrogen oxide when getting in contact with water. Such polymers are for example polyalkyleneimines, such as L-PEI (Linear PolyEthylenelmine) and B-PEI (Branched PolyEthylenelmine), which polymers have the advantage of being biocompatible with natural products, after the release of nitrogen oxide.
Other example for NO eluting polymers are given in U.S. Pat. No. 5,770,645, wherein polymers derivatized with at least one —NOx group per 1200 atomic mass unit of the polymer are disclosed, X being one or two. One example is an S-nitrosylated polymer and is prepared by reacting a polythiolated polymer with a nitrosylating agent under conditions suitable for nitrosylating free thiol groups.
Akron University has developed NO-eluting L-PEI molecule that can be nano-spun onto the surface of medical devices to be permanently implanted in the body, such as implanted grafts, showing significant improvement of the healing process and reduced inflammation when implanting such devices. According to U.S. Pat. No. 6,737,447, a coating for medical devices provides nitric oxide delivery using nanofibers of linear poly (ethylenimine)-diazeniumdiolate. Linear poly (ethylenimine) diazeniumdiolate releases nitric oxide (NO) in a controlled manner to tissues and organs to aid the healing process and to prevent injury to tissues at risk of injury.
However, the meaning of “controlled” in the context of U.S. Pat. No. 6,737,447 is only directed to the fact that nitric oxide is eluted from the coating during a period of time. Therefore, the interpretation of “controlled” in respect of U.S. Pat. No. 6,737,447 is different from the meaning of “regulating” in the present invention. “Regulate”, according to the present invention is intended to be interpreted as the possibility to vary the elution of nitric oxide to thereby achieve different elution profiles.
Electrospun nano-fibers of linear poly (ethylenimine) diazeniumdiolate deliver therapeutic levels of NO for cosmetic purposes to the tissues surrounding a medical device while minimizing the alteration of the properties of the device. A nanofiber coating, because of the small size and large surface area per unit mass of the nanofibers, provides a much larger surface area per unit mass while minimizing changes in other properties of the device.
However, the disclosure is both silent concerning an improvement of present technology in respect of cosmetic treatment of physiologically factors, disorders, such as psoriasis and dermatitis, and viral and/or bacteriological attacks, by the use of NO.
Hence, an improved, and more advantageous, method and device for the treatment and/or prevention of cosmetic disorders is desired. These cosmetic disorders comprise cosmetic disorders, which are caused by chronological age, environmental factors, changes in physiological functions of skin, psoriasis, dermatitis, cellulites, viral and/or bacteriological attacks. It is desired that the method and device do not develop resistance against the active pharmaceutical substance, and which preferably during the cosmetical treatment does not cause or causes minimal local skin irritation or contact allergic reactions, skin toxicity, the requirement of high concentrations of expensive ingredients, pH values that are incompatible with the optimum pH value of the skin, long and cumbersome trials to establish whether or not a specific compound or composition is toxic or not, skin atrophy, telangiectasia, striae, hypertrichosis, rosacea, dermatitis etc, would be advantageous, and in particular a method and device allowing for target improvement of the visual appearance would be advantageous.